DESCRIPTION: (Applicant's Abstract) Marijuana is the most frequently used illicit substance in our society. The neurobiological mechanisms underlying the neuropsychological effects of are still poorly understood, and effective strategies to treat the approximately lOO,OOO individuals admitted to treatment every year for marijuana use are lacking. New evidence suggests that marijuana produces changes in the brain that are similar to those observed following chronic use of harder drugs, implicating marijuana as a possible gateway drug (Tanda et al., 1997 and Rodriguez de Fonseca et al., 1997). Additional research needs to be conducted to assess the impairment of cognitive/decision making abilities, as such impairments may be particularly salient to the potential for escalated drug use. Although several studies have addressed the cognitive effects of marijuana, the anatomical distribution and underlying mechanisms of these effects have received little attention. Therefore, the aims of the proposed study are to use neuroimaging methods: 2-[14C]deoxyglucose, CB1 receptor, and [35S]GTPyS autoradiography (in rodents), as well as functional magnetic resonance imaging (in humans), to (1) investigate the dose-dependent, time-dependent, and residual effects of acute and chronic marijuana on brain activity in the rat using treatment regimens that have previously been associated with cognitive impairment, and to (2) determine the neurobiological substrates directly related to impaired performance of cognitive tasks, demonstrated in humans who frequently use marijuana.